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Antigens

Antineutrophil cytoplasmic antibodies (ANCA) can be subdivided in cytoplasmic ANCA (cANCA) and perinuclear ANCA (pANCA). The main antigen for the cANCA reactivity is the enzyme proteinase 3 (PR3).

PR3 is a cationic protein consisting of 228 amino acids residues and belonging to the trypsin family of serine proteases. Expressed only in primates and humans, PR3 has different functions, including proteolysis of elastin, hemoglobin, fibronectin, laminin and collagen type IV, antimicrobial activities etc.

PR3 in Phadia, now Immunodiagnostics, assays is purified from human neutrophils.

In EliA PR3 S (sensitive) the antigen is coated to the wells with an anchor technique which increases the sensitivity of the test substantially.

When is the measurement recommended?

Presence of more or less typical symptoms such as necrotizing inflammation in the upper airways (GPA), hypereosinophilia with non-allergic asthma (Eosinophillic Glomerulonephritis with Polyangiitis) etc.

Rapidly progressive glomerulonephritis

Presence of symptoms and signs of inflammation such as fever, raised ESR and C-reactive protein level, etc., without identifiable cause or localization

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Antigens

Antineutrophil cytoplasmic antibodies (ANCA) can be subdivided in cytoplasmic ANCA (cANCA) and perinuclear ANCA (pANCA). The main antigen for the pANCA reactivity is the enzyme myeloperoxidase (MPO). MPO is present in and is a marker enzyme of the azurophilic granules of neutrophils. It catalyzes the production of hypochloric acid, which is effective in killing phagocytized bacteria and viruses.

MPO makes up almost 5% of the total protein of a neutrophilic granulocyte. It is a covalently linked dimer with a molecular weight of about 140 kDa.

MPO in Phadia, now Immunodiagnostics, assays is purified from human neutrophils.

In general, anti-MPO and anti-PR3 do not occur in the same patient concurrently. The detection of p-ANCA with clear MPO activity is 99 % specific for necrotizing small vessel vasculitis. In contrast, p-ANCA with negative or low positive MPO reactivity are not associated with vasculitis. A.Wiik, Denmark, suggested that the latter be renamed neutrophil-specific autoantibodies rather than ANCA in order to avoid misinterpretation of results (Carette S., 2004, J Rheumatol 31:792-4).

Disease activity

The relative risk for relapse is increasing with ANCA positivity.

Risk factor for relapse in case of

Relative risk

ANCA positive

10%

ANCA increasing

19%

Stop of treatment

2.4%

Table: ANCA persistence or rise should influence therapeutic decision. (Data from a presentation of Jayne J in Geneva 2002)

ANCA titers are higher during active diseases than at remission.

When is the measurement recommended?

Suspicion of idiopathic systemic vasculitis, which will arise in the following conditions:

Presence of more or less typical symptoms such as necrotizing inflammation in the upper airways (GPA), hypereosinophilia with non-allergic asthma (Eosinophillic Glomerulonephritis with Polyangiitis) etc.

Rapidly progressive glomerulonephritis

Presence of symptoms and signs of inflammation such as fever, raised ESR and C-reactive protein level, etc., without identifiable cause or localization

GBM Antibodies

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The main function of the glomerular basement membrane (GBM) of the kidney is ultrafiltration of blood. Type IV collagen is a typical component of the GBM, has self-aggregating properties and forms a matrix in which the other basement membrane molecules are integrated. Type IV collagen forms trimers that are composed of three subunits of alpha chains. Since the antibodies are directed to epitopes of the so-called "non collagenous domain" (NCI-domain) that are hidden inside the protein in its native structure, there is a need to use denatured antigen for the detection of GBM antibodies.

The Varelisa GBM Antibodies and EliA GBM are the first assays using human recombinant NCI domain of collagen IV alpha 3-chain.

In Goodpasture's syndrome it is important to initiate therapy before renal damage has advanced too far. Early recognition is therefore mandatory and can be confirmed with the use of sensitive assays.

Disease activity

Relatively high antibody titers may persist in patients in clear clinical remission and decline only slowly over a year or so. In general, renal transplantation should be postponed until antibody titration is negative to avoid a recurrence of the disease in the transplant recipient.

When is the measurement recommended?

Suspicion of Goodpasture's Syndrome

Patients with Glomerulonephritis

Positive ANCA results

Before kidney transplantation: Indication of a high risk to go into acute renal failure (poor prognosis)